Designing an Entactin‐Inspired Short Bioactive Hydrogel as Biofunctional Scaffold

Self-assembled peptide hydrogels developed from bioactive domains of extracellular matrix (ECM) have shown great capabilities to mimic the structural and functional aspects of ECM. In this direction, the self-assembling potential of a minimalist bioactive sequence (YWTD) derived from one of the essential bridging proteins of ECM, i.e., entactin, is explored. However, at physiological pH, the negative charge of the aspartate residue induces strong intermolecular repulsion that prevents the self-assembly of the peptide monomers. Interestingly, the peptide forms self-supporting hydrogels at a slightly acidic pH, i.e., pH 6.2, through surface charge neutralization, thereby minimizing the repulsive interaction. Since it is aimed to explore its use in controlling cellular adhesion and proliferation, the buffering capacity of the media is utilized to adjust the pH of the gel to physiological levels. To the best of our knowledge, this is the first report on self-assembly of a novel bioactive sequence derived from the G3 domain of entactin protein. These hydrogels self-assembled at physiological pH display a nanofibrous structure with tuneable mechanical stiffness, which are biocompatible toward fibroblast cells. An improved cellular adhesion and proliferation are evident within this novel matrix, thus proving it as a suitable biomaterial with future potential in the field of biomedicine.